基于网络药理学与分子对接技术的益气散瘀解毒方治疗骨肉瘤的潜在机制分析

Analysis of potential pharmacodynamic mechanism of Yiqi-Sanyu-Jiedu Formula in treatment of osteosarcoma based on network pharmacology and molecular docking

目的探讨益气散瘀解毒方治疗骨肉瘤的活性成分及其潜在作用机制。方法通过TCMSP、TCMID数据库及文献检索查找黄芪、重楼、黄连3味中药的活性成分及作用靶点;利用Genecards、OMIM、TTD数据库获取骨肉瘤相关靶基因;对药物靶点和疾病靶点取交集,运用Cytoscape 3.7.2软件构建“药物-靶点-疾病网络”;通过String数据库获取益气散瘀解毒方治疗骨肉瘤相关蛋白相互作用网络(PPI),利用Network Analyzer工具进行拓扑学分析;利用DAVID数据库对核心靶点进行GO功能富集分析和KEGG通路富集分析;利用AutoDock Vina软件将化合物与骨肉瘤相关蛋白进行分子对接。结果筛选得到益气散瘀解毒方中的共49种活性成分,关键活性成分共23个,治疗骨肉瘤的潜在靶点93个;PPI网络分析得出益气散瘀解毒方治疗骨肉瘤的17个关键靶点蛋白,涉及Akt1、MAPK1、PTGS2和VEGFA等。GO功能富集分析得到GO条目1720个(P<0.05),其中生物过程(BP)条目1583个,细胞组成(CC)条目30个,分子功能(MF)条目107个。KEGG通路富集筛选得到112条信号通路(P<0.05),涉及PI3K-Akt信号通路、MAPK信号通路、HIF-1信号通路等。分子对接结果显示,山柰酚、黄连素和槲皮素与骨肉瘤的Akt1、MAPK1蛋白具有较强的亲和力。结论益气散瘀解毒方中的活性成分可能通过作用于Akt1、MAPK1等靶点,调节多条信号通路,进而起到治疗骨肉瘤的作用。

Objective To explore the active ingredients,targets,potential action mechanism of Yiqi-Sanyu-Jiedu Formula in the treatment of osteosarcoma with network pharmacology and molecular docking technology.Methods All the active ingredients and action targets of astragalus,paris polyphylla and coptis were searched by TCMSP,TCMID and published literatures.Target genes related to osteosarcoma were obtained by Genecards,OMIM and TTD databases.The drug target and disease target were intersected,and the drug-target-disease network was constructed by using Cytoscape 3.7.2.PPI network for the treatment of osteosarcoma with Yiqi-Sanyu-Jiedu Formula was obtained by using the String database,and the Network Analyzer was used for topology analysis.The GO function enrichment analysis were obtainea by and KEGG pathway enrichment andysis of the wre taryets.The compound was molecularly docked with proteins associated with osteosarcoma by using AutoDock Vina.Results:A total of 49 active ingredients and 23 key active ingredients were screened.93 potential targets for the treatment of osteosarcoma were screened.PPI network was used to obtain 42 key target proteins of Yiqi-Sanyu-Jiedu Formula for the treatment of osteosarcoma.The key targets involved Akt1,MAPK1,PTGS2 and VEGFA.GO functional enrichment analysis resulted in 1720 GO items(P<0.05),including 1583 BP items,60 CC items,and 107 MF items.KEGG pathway enrichment analysis resulted in 112 signaling pathways(P<0.05),involving PI3K-Akt signaling pathway,MAPK signaling pathway,and hypoxia-inducible factor-1 signaling pathway.Molecular docking results showed that kaenophenol,berberine and quercetin had strong affinity with Akt1 and MAPK1 proteins of osteosarcoma.Conclusion The active ingredients in Yiqi-Sanyu-Jiedu Formula can act on Akt1,MAPK1 and other targets,so as to regulate multiple signaling pathways and play an important role in the treatment of osteosarcoma.